Similar chemokine receptor profiles in lymphomas with central nervous system involvement - possible biomarkers for patient selection for central nervous system prophylaxis, a retrospective study

• Published in: European journal of haematology 2016-05, Vol.96 (5), p.492-501
• Main Authors: Lemma, Siria A., Pasanen, Anna Kaisa, Haapasaari, Kirsi-Maria, Sippola, Antti, Sormunen, Raija, Soini, Ylermi, Jantunen, Esa, Koivunen, Petri, Salokorpi, Niina, Bloigu, Risto, Turpeenniemi-Hujanen, Taina, Kuittinen, Outi
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers; Case-Control Studies; Central Nervous System Neoplasms - drug therapy; Central Nervous System Neoplasms - metabolism; Central Nervous System Neoplasms - secondary; central nervous system prophylaxis; central nervous system relapse; central nervous system tropism; CXCR4; CXCR5; diffuse large B-cell lymphoma; Endothelial Cells - metabolism; Female; Humans; Immunohistochemistry; Lymph Nodes - metabolism; Lymph Nodes - pathology; Lymphoma - metabolism; Lymphoma - pathology; Lymphoma, Large B-Cell, Diffuse - metabolism; Lymphoma, Large B-Cell, Diffuse - pathology; Male; Middle Aged; Premedication; primary central nervous system lymphoma; Receptors, Chemokine - metabolism; Retrospective Studies; secondary Central nervous system lymphoma
• ISSN: 0902-4441; 1600-0609
• DOI: 10.1111/ejh.12626

Central nervous system (CNS) relapse occurs in around 5% of diffuse large B‐cell lymphoma (DLBCL) cases. No biomarkers to identify high‐risk patients have been discovered. We evaluated the expression of lymphocyte‐guiding chemokine receptors in systemic and CNS lymphomas. Immunohistochemical staining for CXCR4, CXCR5, CCR7, CXCL12, and CXCL13 was performed on 89 tissue samples, including cases of primary central nervous system lymphoma (PCNSL), secondary CNS lymphoma (sCNSL), and systemic DLBCL. Also, 10 reactive lymph node samples were included. Immunoelectron microscopy was performed on two PCNSLs, one sCNSL, one systemic DLBCL, and one reactive lymph node samples, and staining was performed for CXCR4, CXCR5, CXCL12, and CXCL13. Chi‐square test was used to determine correlations between clinical parameters, diagnostic groups, and chemokine receptor expression. Strong nuclear CXCR4 positivity correlated with systemic DLBCL, whereas strong cytoplasmic CXCR5 positivity correlated with CNS involvement (P = 0.003 and P = 0.039). Immunoelectron microscopy revealed a nuclear CXCR4 staining in reactive lymph node, compared with cytoplasmic and membranous localization seen in CNS lymphomas. We found that CNS lymphoma presented a chemokine receptor profile different from systemic disease. Our findings give new information on the CNS tropism of DLBCL and, if confirmed, may contribute to more effective targeting of CNS prophylaxis among patients with DLBCL.